Because treatment for stroke has improved, individuals are living longer with the effects of a stroke. The resulting long-term impairment can affect both stroke survivors' and their caregivers' health-related quality of life (HRQOL). Few studies have examined the HRQOL of stroke survivors and their caregivers greater than 2 years poststroke. The stroke survivors and their spousal caregivers (n = 30 dyads) who had previously completed a 12-month study after discharge from inpatient rehabilitation were assessed at 3-5 years poststroke. The HRQOL and related outcomes were measured for stroke survivors and caregivers. Data from baseline to 12 months were used in conjunction with data from this study. Linear mixed models were used to analyze the change in repeated measures over time. Multiple linear regression was used to analyze the relationship of generic HRQOL to related psychosocial outcomes. The stroke survivors were an average of 4.68 years poststroke. The mean age for stroke survivors and caregivers was 70.8 and 64.9 years, respectively. Most stroke survivors were men (80%) and non-Hispanic White (70%). Among stroke survivors, depression decreased from baseline to 12 months (p = .04) but increased from 12 months to the end of follow-up (p = .003). The caregivers' depression decreased from baseline to all time points (p = .015). Stroke-specific HRQOL showed statistically significant (p < .03) decreases between 12 months and end of follow-up. Increased number of illnesses and older age were associated with caregivers' lower physical HRQOL score (p = .004). Higher depression was associated with lower mental HRQOL score for both caregivers and stroke survivors (p = .003 and p = .011, respectively). Both stroke survivors and caregivers continue to experience negative stroke-related health outcomes for many years after the initial stroke; some of these outcomes even worsen over time. These findings illustrate the need for ongoing psychological and medical evaluation for both long-term stroke survivors and caregivers. Development and testing of targeted behavioral interventions are also warranted.